title: The THO complex component Thp2 counteracts telomeric R-loops and telomere shortening.
abstract: Telomere maintenance by the conventional DNA replication machinery and telomerase is assisted by specialized DNA helicases, nucleases and telomere binding proteins. Here, we identify the THO components at telomeres and define critical roles of this complex in telomere stability. Deletion of the THO-subunit THP2 leads to telomere shortening. We discover that telomeres contain RNA:DNA hybrid structures or R-loops which involve the long-noncoding RNA TERRA and which accumulate in thp2-Δ cells. Telomere length is not restored by R-loop removal upon RNase H overexpression, but by deletion of Exonuclease 1 (Exo1). Replication stress further enhances the short telomere phenotype of THP2 mutants. Similar events occur upon induced transcription of TERRA and genetic analysis links Thp2 to TERRA function. Altogether, our data indicate that THO, through the interplay with TERRA, regulates chromosome end processing activities and prevents interference with semiconservative DNA replication of telomeric DNA.
authors.affiliation: EPFL-Ecole Polytechnique Fédérale de Lausanne, School of Life Sciences, ISREC-Swiss Institute for Experimental Cancer Research, Lausanne, Switzerland.
authors.forename: Verena
authors.initials: V
authors.lastname: Pfeiffer
authors.forename: Jérôme
authors.initials: J
authors.lastname: Crittin
authors.forename: Larissa
authors.initials: L
authors.lastname: Grolimund
authors.forename: Joachim
authors.initials: J
authors.lastname: Lingner
mesh_terms: D004271:DNA, Fungal / Q000235:genetics; D004268:DNA-Binding Proteins / Q000378:metabolism*; D009687:Nuclear Proteins / Q000378:metabolism; D012441:Saccharomyces cerevisiae / Q000235:genetics; D029701:Saccharomyces cerevisiae Proteins / Q000378:metabolism*; D016615:Telomere / Q000737:chemistry / Q000502:physiology*; D059506:Telomere Shortening / Q000235:genetics; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D004271:DNA, Fungal; D004268:DNA-Binding Proteins; C063494:HPR1 protein, S cerevisiae; D009687:Nuclear Proteins; D029701:Saccharomyces cerevisiae Proteins; C405934:THO2 protein, S cerevisiae; C462947:Thp2 protein, S cerevisiae; D014157:Transcription Factors; C068359:MFT1 protein, S cerevisiae